Intensive study of the acetaldehyde-catecholamine condensation reactions in vivo during alcohol metabolism and experimental "alcoholism" in animals is proposed. The tetrahydroisoquinoline (TIQ) alkaloidal products will be detected by sensitive electron capture gas chromatography (ECGC) using an alumina extraction and derivatization method developed in our laoratory. Quantitative changes in neural catecholamines (CAs) during ethanol and methanol intoxication will also be estimated by ECGC. GC components (CAs, Ca metabolites, potential TIQ derivatives) will be subjected to mass spectral analysis or mass fragmentography for positive identification. Animal models of chronic "alcoholism" to be studied will include polydipsic rats and primates such as chimpanzees or rhesus monkeys. CA and AcH levels will be altered by various pharmacological or clinical drugs and any resultant effects on TIQ biosynthesis will be examined by ECGC. Ethanol and AcH levels in blood will be monitored by GC. In addition, an ECGC method for measurement of catecholaldehydes in tissues is to be explored. Synthesis of 4-substituted TIQs, several of interest in alcoholism studies will be continued. The pure substrates will be screened pharmacologically in animals and will be studied for their effects on enzymes associated with CA function and metabolism, such as adenyl cyclase, catechol-O-methyltransferase, and monoamine oxidase.